Surgical excision versus clinical follow-up: Outcomes of benign intraductal papillomas diagnosed on core needle biopsy.

OBJECTIVE: To compare outcomes between benign intraductal papillomas diagnosed on core need biopsy that were excised (BIP-E) versus those that were followed-up (BIP-F) at our institution. METHODS: Patients were identified by an electronic data base search from January 2010 to October 2016. After exclusions, clinical, radiological and histologic variables were evaluated and biopsy and excision slides reviewed. RESULTS: 110 BIP from 104 females were analyzed. 84 BIP were excised and 26 BIP were followed up (mean 43.3 months, range 7-93 months).11 patients in BIP-E group had atypia on excision. There were no statistically significant differences between BIP-E with atypia and BIP-E without, except for clinical presentation with pain/discomfort (p â€‹= â€‹0.015) in the former. There were no true upgrades to malignancy in both groups on follow up. One patient from each group developed a new breast cancer distant from IP site after nearly 4 years of uneventful follow-up. CONCLUSION: Clinical follow up is an oncologically safe alternative for radiologically concordant BIP. Excision may be considered if a diagnosis of atypia would impact surveillence and chemoprevention recommendations.

Synchronous Basal Cell Carcinoma and Squamous Cell Carcinoma of Nasal Vestibule With Novel Unique Variants Identified by Whole-exome Sequencing.

BACKGROUND/AIM: It is estimated that nonmelanoma skin cancer (NMSC), including basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), affects more than 3 million Americans each year. Translation of next-generation sequencing (NGS) data into identification of new potential targets for therapeutic applications may be helpful. Whole-exome sequencing (WES) is a widely used NGS method that involves sequencing the protein-coding regions of the genome. CASE REPORT: We report a case of a 65-year-old female smoker who was found to have two 6 mm lesions in her left nasal vestibule. Biopsies demonstrated synchronous BCC and SCC. The patient underwent surgical excision of both cancers with safe margins followed by plastic reconstruction. WES was performed on both cancers and 16 alterations including BRCA2 (p.P389S), FAM5C (S420L), KMT2A (P855L), and SMO (L412F), as unique for BCC, and 4 alterations including TP53 (p.H179Q) and CDKN2A (p.P114L), as unique for SCC, were identified. CONCLUSION: We report the first documented case with unique genetic alterations in two distinct and synchronous skin BCC and SCC arising from the same nasal vestibule of a patient. This adds to the growing field of data regarding genetic variants in characterizing malignancies and potentially for targeted therapies.

Distinct Single Cell Gene Expression in Peripheral Blood Monocytes Correlates With Tumor Necrosis Factor Inhibitor Treatment Response Groups Defined by Type I Interferon in Rheumatoid Arthritis.

Previously, we demonstrated in test and validation cohorts that type I IFN (T1IFN) activity can predict non-response to tumor necrosis factor inhibitors (TNFi) in rheumatoid arthritis (RA). In this study, we examine the biology of non-classical and classical monocytes from RA patients defined by their pre-biologic treatment T1IFN activity. We compared single cell gene expression in purified classical (CL, n = 342) and non-classical (NC, n = 359) monocytes. In our previous work, RA patients who had either high IFNß/α activity (>1.3) or undetectable T1IFN were likely to have EULAR non-response to TNFi. In this study comparisons were made among patients grouped according to their pre-biologic treatment T1IFN activity as clinically relevant: "T1IFN undetectable (T1IFN ND) or IFNß/α >1.3" (n = 9) and "T1IFN detectable but IFNß/α ≤ 1.3" (n = 6). In addition, comparisons were made among patients grouped according to their T1IFN activity itself: "T1IFN ND," "T1IFN detected and IFNß/α ≤ 1.3," and "IFNß/α >1.3." Major differences in gene expression were apparent in principal component and unsupervised cluster analyses. CL monocytes from the T1IFN ND or IFNß/α >1.3 group were unlikely to express JAK1 and IFI27 (p < 0.0001 and p 0.0005, respectively). In NC monocytes from the same group, expression of IFNAR1, IRF1, TNFA, TLR4 (p ≤ 0.0001 for each) and others was enriched. Interestingly, JAK1 expression was absent in CL and NC monocytes from nine patients. This pattern most strongly associated with the IFNß/α>1.3 group. Differences in gene expression in monocytes among the groups suggest differential IFN pathway activation in RA patients who are either likely to respond or to have no response to TNFi. Additional transcripts enriched in NC cells of those in the T1IFN ND and IFNß/α >1.3 groups included MYD88, CD86, IRF1, and IL8. This work could suggest key pathways active in biologically defined groups of patients, and potential therapeutic strategies for those patients unlikely to respond to TNFi.

Desmoplasia and Detached Papillae in Early Esophageal Adenocarcinoma: A Histologic Study on Endoscopic Submucosal Dissection Specimens.

BACKGROUND: Desmoplasia and detached papillae were only rarely mentioned in intramucosal adenocarcinoma of esophagus or stomach. This study aimed to examine these two features in early esophageal adenocarcinoma. METHODS: All endoscopic submucosal dissections specimens performed for Barrett's esophagus neoplasm during the year 2013 to 2016 were reviewed. These 44 cases included in this study were eight Barrett's esophagus with high-grade dysplasia, 21 intramucosal adenocarcinoma, and 15 submucosally or beyond invasive adenocarcinoma. RESULTS: Desmoplasia occurred in 73% submucosally or beyond invasive adenocarcinoma, higher than intramucosal adenocarcinoma (24%) and high-grade dysplasia (0%) (P < 0.00001 for each). The frequency of detached papillae in intramucosal adenocarcinoma and submucosally or beyond invasive adenocarcinoma specimens was 71.4% and 73.3%, higher than high-grade dysplasia (0%, P < 0.0001 for both). Univariate analysis identified desmoplasia as risk factors for lymphovascular invasion in intramucosal adenocarcinoma specimens (odds ratio 12, P = 0.048), and desmoplasia and tumor thickness for lymphovascular invasion in intramucosal adenocarcinoma and submucosally or beyond invasive adenocarcinoma specimens combined (odds ratio 9.0, P = 0.005; odds ratio 2.7, P = 0.01, respectively). Age, gender, the largest dimension and the average thickness of endoscopic submucosal dissection specimens, tumor size, detached papillae, and poor differentiation were not associated with lymphovascular invasion (P ≥ 0.05 for all). Multivariate analysis confirmed that only desmoplasia was predictive of lymphovascular invasion (odds ratio 8.0, P = 0.02) in intramucosal adenocarcinoma and submucosally or beyond invasive adenocarcinoma specimens combined. CONCLUSIONS: In conclusion, desmoplasia occurs in about a quarter of esophageal intramucosal adenocarcinomas and three quarters of submucosally or beyond invasive adenocarcinomas, and is associated with lymphovascular invasion in early esophageal adenocarcinoma.